Lung cancer
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{{Infobox_Disease |
Name = Lung cancer |
Image = cancerous_lung.jpg |
Caption = Cross section of a human lung. The white area in the upper lobe is cancer; the black areas indicate that the patient was a [[Tobacco smoking|smoker]]. |
DiseasesDB = 7616 |
ICD10 = {{ICD10|C|33||c|30}}-{{ICD10|C|34||c|30}} |
ICD9 = {{ICD9|162}} |
ICDO = |
OMIM = |
MedlinePlus = 007194 |
eMedicineSubj = med |
eMedicineTopic = 1333 |
eMedicine_mult = {{eMedicine2|med|1336}} {{eMedicine2|emerg|335}} {{eMedicine2|radio|807}} {{eMedicine2|radio|405}} {{eMedicine2|radio|406}} |
MeshID = D002283 |
}}
'''Lung cancer''' is a [[disease]] of uncontrolled [[cell growth]] in [[tissue (biology)|tissues]] of the [[lung]]. This growth may lead to [[metastasis]], invasion of adjacent tissue and infiltration beyond the lungs. The vast majority of primary lung cancers are '''carcinomas of the lung''', derived from [[epithelium|epithelial]] cells. Lung [[cancer]], the most common cause of cancer-related death in men and the second most common in women,<ref name="WHO2">{{cite web | author=WHO | authorlink =World Health Organization | title =Deaths by cause, sex and mortality stratum | publisher =[[World Health Organization]] | date =2004 | url=http://www.who.int/whr/2004/annex/topic/en/annex_2_en.pdf | format = PDF| accessdate =2007-06-01 }}</ref><ref name="NLCP">{{cite web | authorlink = | coauthors = | title =Lung Cancer Facts (Women) | publisher = National Lung Cancer Partnership | date =2006 | url =http://www.nationallungcancerpartnership.org/page.cfm?l=factsWomen | accessdate =2007-05-26 }}</ref> is responsible for [[:Category:Lung cancer deaths|1.3 million deaths]] worldwide
annually.<ref name="WHO">{{cite web | author =WHO | authorlink =World Health Organization | title =Cancer | publisher =[[World Health Organization]] | date=February 2006 | url=http://www.who.int/mediacentre/factsheets/fs297/en/ | accessdate =2007-06-25 }}</ref> In the UK, it is the most common site of fatal cancer in both men and women. The most common [[symptom]]s are shortness of breath, coughing (including [[Hemoptysis|coughing up blood]]), and weight loss.<ref name="Harrison">{{cite book | last=Minna | first=JD | title=Harrison's Principles of Internal Medicine | publisher=McGraw-Hill | date =2004 | pages =506–516 | doi=10.1036/0071402357 | isbn=0071391401 }}</ref>
The main types of lung cancer are ''small cell lung carcinoma'' and ''non-small cell lung carcinoma''. This distinction is important because the treatment varies; non-small cell lung carcinoma (NSCLC) is sometimes treated with [[lung cancer surgery|surgery]], while small cell lung carcinoma (SCLC) usually responds better to [[chemotherapy]] and radiation.<ref name="Cancer Medicine"/> The most common cause of lung cancer is long term exposure to [[tobacco smoking|tobacco smoke]].<ref name="Merck"/> The occurrence of lung cancer in non-smokers, who account for as many as 20% of cases, often attributed to a combination of [[genetics|genetic factors]],<ref name="Gorlova">{{cite journal | last =Gorlova | first =OY | coauthors =Weng SF, Zhang Y et al. | title =Aggregation of cancer among relatives of never-smoking lung cancer patients | journal = International Journal of Cancer | volume = 121 | issue = 1 | pages = 111–118 | date =July 2007 | pmid =17304511 | doi =10.1002/ijc.22615 }}</ref><ref name="Hackshaw">{{cite journal | last =Hackshaw | first =AK | coauthors =Law MR, Wald NJ | title =The accumulated evidence on lung cancer and environmental tobacco smoke | journal =British Medical Journal | volume =315 | issue =7114 | pages =980–988 | date =October 1997 | url =http://www.bmj.com/cgi/content/full/315/7114/980 | pmid =9365295 }}</ref> [[radon]] gas,<ref name="Catelinois"/> [[asbestos]],<ref name="O'Reilly"/> and [[air pollution]],<ref name="Kabir">{{cite journal | last = Kabir | first = Z | coauthors = Bennett K, Clancy L | title = Lung cancer and urban air-pollution in dublin: a temporal association? | journal = Irish Medical Journal | volume = 100 | issue = 2 | pages = 367–369 | date =February 2007 | pmid =17432813 }}</ref><ref name="Coyle">{{cite journal | last = Coyle | first = YM | coauthors = Minahjuddin AT, Hynan LS, Minna JD | title = An ecological study of the association of metal air pollutants with lung cancer incidence in Texas. | journal = Journal of Thoracic Oncology | volume = 1 | issue = 7 | pages = 654–661 | date =September 2006 | pmid =17409932 }}</ref><ref name="Chiu">{{cite journal | last = Chiu | first = HF | coauthors = Cheng MH, Tsai SS et al. | title = Outdoor air pollution and female lung cancer in Taiwan. | journal = Inhalation Toxicology | volume = 18 | issue = 13 | pages = 1025–1031 | date = December 2006 | pmid =16966302 | doi = 10.1080/08958370600904561 }}</ref> including [[passive smoking|second-hand smoke]].<ref>{{cite web |url=http://www.surgeongeneral.gov/library/secondhandsmoke |author=Carmona Richard H. |publisher=U.S. Department of Health and Human Services |title=The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General |date=2006-06-27 |quote=Secondhand smoke exposure causes disease and premature death in children and adults who do not smoke.}}</ref><ref>{{cite journal |url=http://monographs.iarc.fr/ENG/Monographs/vol83/volume83.pdf |format=PDF |publisher=WHO International Agency for Research on Cancer |title=Tobacco Smoke and Involuntary Smoking |journal=IARC Monographs on the Evaluation of Carcinogenic Risks to Humans |volume=83 |year=2002 |quote=There is sufficient evidence that involuntary smoking (exposure to secondhand or 'environmental' tobacco smoke) causes lung cancer in humans. [...] Involuntary smoking (exposure to secondhand or 'environmental' tobacco smoke) is carcinogenic to humans (Group 1).}}</ref>
Lung cancer may be seen on [[chest x-ray]] and [[computed tomography]] (CT scan). The [[diagnosis]] is confirmed with a [[biopsy]]. This is usually performed via [[bronchoscopy]] or CT-guided biopsy. Treatment and [[prognosis]] depend upon the [[histology|histological]] type of cancer, the [[staging (pathology)|stage]] (degree of spread), and the patient's [[performance status]]. Possible treatments include surgery, chemotherapy, and [[radiation therapy|radiotherapy]]. With treatment, the five-year [[survival rate]] is 14%.<ref name="Harrison"/>
== Classification ==
{| class="wikitable floatright" style="text-align:center;font-size:90%;width:45%;margin-left:1em"
|+ style="font-size:90%;background:#E5AFAA;"|'''Frequency of histological types of lung cancer'''<ref name="Travis"/>
|- style="background: #E5AFAA;text-align:center;font-size:90%;"
! abbr="Type" | Histological type
! abbr="Frequency" | Frequency (%)
|-
| Non-small cell lung carcinoma
| 80.4
|-
| Small cell lung carcinoma
| 16.8
|-
| [[Carcinoid]]<ref>{{cite journal | last =Morandi | first =U | coauthors =Casali C, Rossi G | title =Bronchial typical carcinoid tumors | journal =Seminars in Thoracic and Cardiovascular Surgery | volume =18 | issue =3 | pages =191–198 | date =2006 | pmid =17185178 | doi =10.1053/j.semtcvs.2006.08.005 }}</ref>
| 0.8
|-
| [[Sarcoma]]<ref>{{cite journal | last =Etienne-Mastroianni | first =B | coauthors = Falchero L, Chalabreysse L et al. | title =Primary sarcomas of the lung: a clinicopathologic study of 12 cases | journal =Lung Cancer | volume =38 | issue =3 | pages =283–289 | date =December 2002 | pmid =12445750 | doi =10.1016/S0169-5002(02)00303-3 }}</ref>
| 0.1
|-
| Unspecified lung cancer
| 1.9
|}
The vast majority of lung cancers are [[carcinoma]]s—malignancies that arise from [[epithelial cell]]s. There are two main types of lung carcinoma, categorized by the size and appearance of the malignant cells seen by a [[histopathology|histopathologist]] under a [[microscope]]: ''non-small cell'' (80.4%) and ''small-cell'' (16.8%) lung carcinoma.<ref name="Travis">{{cite journal | last =Travis | first =WD | coauthors =Travis LB, Devesa SS | title =Lung cancer | journal =Cancer | volume =75 | issue =Suppl. 1 | pages =191–202 | date =January 1995 | pmid =8000996| doi =10.1002/1097-0142(19950101)75:1 <191::AID-CNCR2820751307>3.0.CO;2-Y }}</ref> This classification, based on [[histology|histological]] criteria, has important implications for clinical management and prognosis of the disease.
==== Non-small cell lung carcinoma (NSCLC) ====
The non-small cell lung carcinomas are grouped together because their prognosis and management are similar. There are three main sub-types: [[squamous cell carcinoma|squamous cell lung carcinoma]], [[adenocarcinoma]] and large cell lung carcinoma.
{| class="wikitable floatright" style="text-align:center;font-size:90%;width:45%;margin-left:1em"
|+ style="font-size:90%;background:#E5AFAA;"|'''Sub-types of non-small cell lung cancer'''<ref name="Travis"/>
|- style="background: #E5AFAA;text-align:center;font-size:90%;"
! colspan="2" abbr="Sub-type" | Histological sub-type
! abbr="Frequency" | Frequency of all lung cancers (%)
|-
| colspan="2" | Squamous cell lung carcinoma
| 31.1
|-
| rowspan="7" valign="top" | Adenocarcinoma
| Adenocarcinoma (not otherwise specified)
| 23.2
|-
| [[Bronchioloalveolar carcinoma]]
| 3.0
|-
| Adenosquamous carcinoma
| 1.2
|-
| Papillary adenocarcinoma
| 0.7
|-
| Mucoepidermoid carcinoma<ref>{{cite journal | last =Sánchez-Mora | first =N | coauthors =Parra-Blanco V, Cebollero-Presmanes M et al. | title =Mucoepidermoid tumors of the bronchus. Ultrastructural and immunohistochemical study | journal =Histology and Histopathology | volume =22 | issue =1 | pages =9–13 | date =January 2007 | pmid =17128406 }}</ref>
| 0.1
|-
| Adenoid cystic carcinoma<ref>{{cite journal | last =Moran | first =CA | coauthors =Suster S, Koss MN | title =Primary adenoid cystic carcinoma of the lung. A clinicopathologic and immunohistochemical study of 16 cases | journal =Cancer | volume =73 | issue =5 | pages =1390–1397 | date =March 1994 | pmid =7509254 | doi =10.1002/1097-0142(19940301)73:5<1390::AID-CNCR2820730513>3.0.CO;2-# }}</ref>
| 0.04
|-
| Other specified adenocarcinoma
| 1.1
|-
| colspan="2" | Large cell carcinoma
| 10.7
|-
| colspan="2" | Giant cell and spindle cell carcinoma
| 0.4
|-
| colspan="2" | Other/unspecified non-small cell lung carcinoma
| 8.9
|}
Accounting for 31.1% of lung cancers,<ref name="Travis"/> squamous cell lung carcinoma usually starts near a central [[bronchus]]. [[Cavitation]] and [[necrosis]] within the center of the cancer is a common finding. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types.<ref name="Cancer Medicine">{{cite book | last =Vaporciyan | first =AA | coauthors =Nesbitt JC, Lee JS et al. | title =Cancer Medicine | publisher=B C Decker | date =2000 | pages =1227–1292 | isbn =1-55009-113-1 }}</ref>
Adenocarcinoma accounts for 29.4% of lung cancers.<ref name="Travis"/> It usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking. However, among people who have never smoked ("never-smokers"), adenocarcinoma is the most common form of lung cancer.<ref name="Subramanian">{{cite journal | last =Subramanian | first =J | coauthors =Govindan R | title =Lung cancer in never smokers: a review | journal =Journal of Clinical Oncology | volume =25 | issue =5 | pages =561–570 | publisher =American Society of Clinical Oncology | date =February 2007 | pmid =17290066 | doi =10.1200/JCO.2006.06.8015 }}</ref> A subtype of adenocarcinoma, the [[bronchioloalveolar carcinoma]], is more common in female never-smokers, and may have different responses to treatment.<ref name="Raz">{{cite journal | last =Raz | first =DJ | coauthors =He B, Rosell R, Jablons DM | title =Bronchioloalveolar carcinoma: a review | journal =Clinical Lung Cancer | volume =7 | issue =5 | pages =313–322 | publisher =Cancer Information Group | date =March 2006 | pmid =16640802 }}</ref>
Accounting for 10.7% of lung cancers,<ref name="Travis"/> large cell lung carcinoma is a fast-growing form that develops near the surface of the lung.<ref name="Veronesi">{{cite journal | author=Veronesi G | coauthors= Morandi U, Alloisio M et al. | title=Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases | journal=Lung Cancer | volume=53 | issue=1 | pages=111–115 | date =July 2006 | pmid=16697073 | doi=10.1016/j.lungcan.2006.03.007 }}</ref> It is often poorly [[cellular differentiation|differentiated]] and tends to [[metastasis|metastasize]] early.<ref name="Cancer Medicine"/>
==== Small cell lung carcinoma (SCLC) ====
[[Image:Lung small cell carcinoma (1) by core needle biopsy.jpg|thumb|left|Small cell lung carcinoma (microscopic view of a core needle biopsy)]]
[[Small cell lung carcinoma]] (SCLC, also called "oat cell carcinoma") is less common. It tends to arise in the larger airways (primary and secondary [[bronchus|bronchi]]) and grows rapidly, becoming quite large.<ref name="Collins"/> The "oat" cell contains dense neurosecretory granules ([[vesicle (biology)|vesicles]] containing [[neuroendocrine]] [[hormone]]s) which give this an endocrine/paraneoplastic syndrome association.<ref name="Rosti">{{cite journal | last=Rosti | first=G | coauthors=Bevilacqua G, Bidoli P et al. | title=Small cell lung cancer | journal=Annals of Oncology | volume=17 | issue=Suppl. 2 | pages=5–10 | date =March 2006 | url=http://annonc.oxfordjournals.org/cgi/reprint/17/suppl_2/ii5 | pmid=16608983 | doi=10.1093/annonc/mdj910 }}</ref> While initially more sensitive to chemotherapy, it ultimately carries a worse prognosis and is often metastatic at presentation. Small cell lung cancers are divided into Limited stage and Extensive stage disease. This type of lung cancer is strongly associated with smoking.<ref name="Barbone">{{cite journal | last =Barbone | first =F | coauthors=Bovenzi M, Cavallieri F, Stanta G | title =Cigarette smoking and histologic type of lung cancer in men | journal =Chest | volume =112| issue=6 | pages =1474–1479 | publisher =American College of Chest Physicians | date =December 1997 | url =http://www.chestjournal.org/cgi/reprint/112/6/1474 | format = PDF | pmid = 9404741 | doi =10.1378/chest.112.6.1474 }}</ref>
==== Metastatic cancers ====
The lung is a common place for [[metastasis]] from tumors in other parts of the body. These cancers are identified by the site of origin, thus a breast cancer metastasis to the lung is still known as breast cancer. They often have a characteristic round appearance on chest x-ray.<ref name="Seo">{{cite journal | last =Seo | first =JB | coauthors=Im JG, Goo JM et al. | title =Atypical pulmonary metastases: spectrum of radiologic findings | journal =Radiographics | volume =21 | issue=2 | pages =403–417 | date =2001 | url =http://radiographics.rsnajnls.org/cgi/content/full/21/2/403 | pmid = 11259704 }}</ref> Primary lung cancers themselves most commonly metastasize to the [[adrenal gland]]s, liver, brain, and bone.<ref name="Cancer Medicine"/>
=== Staging ===
{{see also|Non-small cell lung carcinoma staging|lung cancer staging with EUS}}
Lung [[cancer staging]] is an assessment of the degree of spread of the cancer from its original source. It is an important factor affecting the [[prognosis]] and potential treatment of lung cancer. Non-small cell lung carcinoma is staged from IA ("one A", best prognosis) to IV ("four", worst prognosis).<ref>{{cite book | last =Mountain | first =CF | authorlink = | coauthors =Libshitz HI, Hermes KE | title =A Handbook for Staging, Imaging, and Lymph Node Classification | publisher =Charles P Young | date =2003 | url =http://www.ctsnet.org/book/mountain/index.html | accessdate =2007-09-01 }}</ref> Small cell lung carcinoma is classified as ''limited stage'' if it is confined to one half of the chest and within the scope of a single [[radiotherapy]] field. Otherwise it is ''extensive stage''.<ref name="Collins">{{cite journal | last = Collins | first = LG | coauthors = Haines C, Perkel R, Enck RE | title = Lung cancer: diagnosis and management | journal = American Family Physician | volume = 75 | issue = 1 | pages = 56–63 | publisher = American Academy of Family Physicians | date = January 2007 | url= http://www.aafp.org/afp/20070101/56.html | pmid =17225705 }}</ref>
==Signs and symptoms==
[[Symptom]]s that suggest lung cancer include:<ref name="Hamilton">{{cite journal | last=Hamilton | first=W | coauthors=Peters TJ, Round A, Sharp D | title=What are the clinical features of lung cancer before the diagnosis is made? A population based case-control study | journal =Thorax | volume =60 | issue=12 | pages=1059–1065 | publisher=BMJ Publishing Group | date=December 2005 | pmid=16227326 | doi=10.1136/thx.2005.045880 }}</ref>
<div class="references-small" style="-moz-column-count:3; column-count:3;">
* [[dyspnea]] (shortness of breath)
* [[hemoptysis]] (coughing up blood)
* chronic [[coughing]] or change in regular coughing pattern
* wheezing
* [[chest pain]] or pain in the abdomen
* [[cachexia]] (weight loss), [[Fatigue (physical)|fatigue]] and loss of [[appetite]]
* [[dysphonia]] (hoarse voice)
* [[clubbing]] of the fingernails (uncommon)
* [[dysphagia]] (difficulty swallowing).
</div>
If the cancer grows in the [[airway]], it may obstruct airflow, causing [[dyspnea|breathing difficulties]]. This can lead to accumulation of secretions behind the blockage, predisposing the patient to [[pneumonia]]. Many lung cancers have a rich blood supply. The surface of the cancer may be fragile, leading to bleeding from the cancer into the airway. This blood may subsequently be coughed up.
Depending on the type of tumor, so-called [[Paraneoplastic syndrome|paraneoplastic phenomena]] may initially attract attention to the disease.<ref name="Honnorat">{{cite journal | last=Honnorat | first=J | coauthors=Antoine JC | title=Paraneoplastic neurological syndromes | journal=Orphanet Journal of Rare Diseases | volume=2 | pages=22 | publisher=BioMed Central | date=May 2007 | url=http://www.ojrd.com/content/2/1/22 | pmid=17480225 | doi=10.1186/1750-1172-2-22 }}</ref> In lung cancer, these phenomena may include [[Lambert-Eaton myasthenic syndrome]] (muscle weakness due to [[autoimmune disorder|auto-antibodies]]), [[hypercalcemia]] or [[syndrome of inappropriate antidiuretic hormone]] (SIADH). Tumors in the top (apex) of the lung, known as [[Pancoast tumor]]s,<ref name="Jones">{{cite journal | last=Jones | first=DR | coauthors=Detterbeck FC | title=Pancoast tumors of the lung | journal=Current Opinion in Pulmonary Medicine | volume=4 | issue=4 | pages=191–197 | date=July 1998 | pmid=10813231 | doi=10.1097/00063198-199807000-00001 }}</ref> may invade the local part of the [[sympathetic nervous system]], leading to changed sweating patterns and eye muscle problems (a combination known as [[Horner's syndrome]]), as well as muscle weakness in the hands due to invasion of the [[brachial plexus]].
Many of the symptoms of lung cancer ([[bone pain]], [[fever]], [[weight loss]]) are nonspecific; in the elderly, these may be attributed to [[comorbidity|comorbid illness]].<ref name="Cancer Medicine"/> In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of [[metastasis]] include the bone, such as the [[Vertebral column|spine]] (causing back pain and occasionally [[spinal cord compression]]), the liver and the brain. About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest x-rays.<ref name="Harrison"/>
=== Causes ===
The main causes of lung cancer (and cancer in general) include [[carcinogen]]s (such as those in tobacco smoke), [[ionizing radiation]], and [[virus (biology)|viral]] infection. This exposure causes cumulative changes to the [[DNA]] in the tissue lining the [[bronchi]] of the lungs (the bronchial [[epithelium]]). As more tissue becomes damaged, eventually a cancer develops.<ref name="Cancer Medicine"/>
===Smoking===
[[Image:Cancer smoking lung cancer correlation from NIH.svg|thumb|300px|right|The incidence of lung cancer is highly correlated with smoking. Source: NIH.]]
[[Tobacco smoking|Smoking]], particularly of [[cigarette]]s, is by far the main contributor to lung cancer.<ref>{{cite journal |author=Biesalski HK, Bueno de Mesquita B, Chesson A, ''et al'' |title=European Consensus Statement on Lung Cancer: risk factors and prevention. Lung Cancer Panel |journal=CA Cancer J Clin |volume=48 |issue=3 |pages=167–176; discussion 164–166 |year=1998 |pmid=9594919 |url=http://caonline.amcancersoc.org/cgi/pmidlookup?view=long&pmid=9594919 |quotation=Smoking is the major risk factor, accounting for about 90% of lung cancer incidence. |doi=10.3322/canjclin.48.3.167}}</ref> Across the developed world, almost 90% of lung cancer deaths are caused by smoking.<ref name="Peto">{{cite book | last=Peto R | first=R | coauthors=Lopez AD, Boreham J et al. | title=Mortality from smoking in developed countries 1950–2000: Indirect estimates from National Vital Statistics | publisher=Oxford University Press | date=2006 | url=http://www.ctsu.ox.ac.uk/~tobacco/ | isbn=0-19-262535-7 }}</ref> In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women).<ref name="Samet2">{{cite journal | last=Samet | first=JM | coauthors=Wiggins CL, Humble CG, Pathak DR | title=Cigarette smoking and lung cancer in New Mexico | journal=American Review of Respiratory Disease | volume=137 | issue=5 | pages=1110–1113 | date=May 1988 | pmid=3264122 }}</ref> Among male smokers, the lifetime risk of developing lung cancer is 17.2%. Among female smokers, the risk is 11.6%. This risk is significantly lower in non-smokers: 1.3% in men and 1.4% in women.<ref name="Villeneuve">{{cite journal | last=Villeneuve | first=PJ | coauthors=Mao Y | title=Lifetime probability of developing lung cancer, by smoking status, Canada | journal=Canadian Journal of Public Health | volume=85 | issue=6 | pages=385–388 | date=November 1994 | pmid=7895211 }}</ref> Cigarette smoke contains over 60 known carcinogens<ref name="Hecht">{{cite journal | last=Hecht | first=S | title=Tobacco carcinogens, their biomarkers and tobacco-induced cancer | journal=Nature Reviews. Cancer | volume=3 | issue=10 | pages=733–744 | publisher=Nature Publishing Group | date=October 2003 | url=http://www.nature.com/nrc/journal/v3/n10/abs/nrc1190_fs.html;jsessionid=A78B217DFCAD36DD965F2DBA685CF121 | doi=10.1038/nrc1190 | pmid=14570033 }}</ref> including [[radioisotopes]] from the [[radon]] decay sequence, [[nitrosamine]], and [[benzopyrene]]. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue.<ref>{{cite journal | last=Sopori | first=M | title=Effects of cigarette smoke on the immune system | journal=Nature Reviews. Immunology | volume=2 | issue=5 | pages=372–7 | date=May 2002 | pmid=12033743 | doi=10.1038/nri803 }}</ref>
The length of time a person smokes as well as the amount smoked increases the person's chance of developing lung cancer. If a person stops smoking, this chance steadily decreases as damage to the lungs is repaired and contaminant particles are gradually removed.<ref name="USDHHS1990">{{citation | author=US Department of Health and Human Services | title=The Health Benefits of Smoking Cessation: a Report of the [[Surgeon General]] | publisher=Centers for Disease Control (CDC), Office on Smoking and Health. | year=1990 | url=http://profiles.nlm.nih.gov/NN/B/B/C/T/_/nnbbct.pdf | format=PDF | pages=vi, 130, 148, 152, 155, 164, 166 | accessdate=2007-11-18 | date=1990-09-30 }}</ref> In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers,<ref name="Nordquist">{{cite journal | last=Nordquist | first=LT | coauthors=Simon GR, Cantor A et al. | title=Improved survival in never-smokers vs current smokers with primary adenocarcinoma of the lung | journal=Chest | volume=126 | issue=2 | pages=347–351 | publisher=American College of Chest Physicians | date=August 2004 | url=http://www.chestjournal.org/cgi/content/full/126/2/347 | pmid=15302716 | doi=10.1378/chest.126.2.347 }}</ref> and that patients who smoke at the time of diagnosis have shorter survival than those who have quit.<ref name="Tammemagi">{{cite journal | last=Tammemagi | first=CM | coauthors=Neslund-Dudas C, Simoff M, Kvale P | title=Smoking and lung cancer survival: the role of comorbidity and treatment | journal=Chest | volume=125 | issue=1 | pages=27–37 | publisher=American College of Chest Physicians | date=January 2004 | url=http://www.chestjournal.org/cgi/content/full/125/1/27 | pmid=14718417 | doi=10.1378/chest.125.1.27 }}</ref>
[[Passive smoking]]—the inhalation of smoke from another's smoking—is a cause of lung cancer in non-smokers. Studies from the U.S.,<ref>{{cite web | last=CDC | authorlink=Centers for Disease Control and Prevention | title=1986 Surgeon General's report: the health consequences of involuntary smoking | publisher=CDC | date=December 1986 | url=http://www.cdc.gov/mmwr/preview/mmwrhtml/00000837.htm | pmid=3097495 | accessdate=2007-08-10 }}<br />* {{cite book | last=National Research Council | title=Environmental tobacco smoke: measuring exposures and assessing health effects | publisher=National Academy Press | date=1986 | url=http://www.nap.edu/catalog.php?record_id=943#toc | isbn=0-309-07456-8 }}<br />* {{cite paper | author=EPA | authorlink=United States Environmental Protection Agency | title=Respiratory health effects of passive smoking: lung cancer and other disorders | publisher=EPA | date=1992 | url=http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=2835 | accessdate=2007-08-10 }}<br />* {{cite journal | last=California Environmental Protection Agency | title=Health effects of exposure to environmental tobacco smoke |journal=Tobacco Control | volume=6 | issue=4 | pages=346–353 | date=1997 | url=http://www.druglibrary.org/schaffer/tobacco/caets/ets-main.htm | pmid=9583639 }}<br />* {{cite journal | last=CDC | authorlink=Centers for Disease Control and Prevention | title=State-specific prevalence of current cigarette smoking among adults, and policies and attitudes about secondhand smoke—United States, 2000 | journal=Morbidity and Mortality Weekly Report | volume=50 | issue=49 | pages=1101–1106 | publisher=CDC |location=Atlanta, Georgia| date=December 2001 | url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5049a1.htm | pmid=11794619 }}<br />* {{cite journal | last=Alberg | first=AJ | coauthors=Samet JM | title=Epidemiology of lung cancer | journal=Chest | volume=123 | issue=S1 | pages=21S–49S | publisher=American College of Chest Physicians | date=January 2003 | url=http://www.chestjournal.org/cgi/content/full/123/1_suppl/21S | pmid=12527563 | doi=10.1378/chest.123.1_suppl.21S }}</ref> Europe,<ref name="Boffetta">{{cite journal | last=Boffetta | first=P | coauthors=Agudo A, Ahrens W et al. | title=Multicenter case-control study of exposure to environmental tobacco smoke and lung cancer in Europe | journal=Journal of the National Cancer Institute | volume=90 | issue=19 | pages=1440–1450 | publisher=Oxford University Press | date=October 1998 | url=http://jnci.oxfordjournals.org/cgi/reprint/90/19/1440 | pmid=9776409 | doi=10.1093/jnci/90.19.1440 }}</ref> the UK,<ref name="Committee">{{cite web | title=Report of the Scientific Committee on Tobacco and Health | publisher=Department of Health | date=March 1998 | url=http://www.archive.official-documents.co.uk/document/doh/tobacco/contents.htm | accessdate=2007-07-09 }}<br />* {{cite journal | last=Hackshaw | first=AK | title=Lung cancer and passive smoking | journal=Statistical Methods in Medical Research | volume=7 | issue=2 | pages=119–136 | date=June 1998 | pmid=9654638 | doi=10.1191/096228098675091404 }}</ref> and Australia<ref name="NHMRC">{{cite paper | author=National Health and Medical Research Council | title=The health effects and regulation of passive smoking | publisher=Australian Government Publishing Service | date=April 1994 | url=http://www.obpr.gov.au/publications/submission/healthef/index.html | accessdate=2007-08-10 }}</ref> have consistently shown a significant increase in [[relative risk]] among those exposed to passive smoke. Recent investigation of [[sidestream smoke]] suggests it is more dangerous than direct smoke inhalation.<ref name="Schick">{{cite journal | last=Schick | first=S | coauthors=Glantz S | title=Philip Morris toxicological experiments with fresh sidestream smoke: more toxic than mainstream smoke | journal=Tobacco Control | volume=14 | issue=6 | pages=396–404 | date=December 2005 | pmid=16319363 | doi=10.1136/tc.2005.011288 }}</ref>
===Radon gas===
[[Radon]] is a colorless and odorless [[gas]] generated by the breakdown of radioactive [[radium]], which in turn is the decay product of [[uranium]], found in the earth's [[Crust (geology)|crust]]. The radiation decay products [[ion]]ize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer after smoking.<ref name="Catelinois">{{cite journal | last =Catelinois | first =O | coauthors = Rogel A, Laurier D et al. | title=Lung Cancer Attributable to Indoor Radon Exposure in France: Impact of the Risk Models and Uncertainty Analysis | journal =Environmental Health Perspectives | volume =114 | issue =9 | pages =1361–1366 | publisher =National Institute of Environmental Health Science | date =May 2006 | url =http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16966089 | doi =10.1289/ehp.9070 | pmid =16966089 }}</ref> Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as [[Cornwall]] in the UK (which has [[granite]] as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The [[United States Environmental Protection Agency]] (EPA) estimates that one in 15 homes in the U.S. has radon levels above the recommended guideline of 4 [[picocurie]]s per liter (pCi/L) (148 [[becquerel|Bq]]/[[cubic metre|m³]]).<ref name="EPA radon">{{cite web | last =EPA | authorlink =United States Environmental Protection Agency | title =Radiation information: radon | publisher =EPA | date =October 2006 | url =http://www.epa.gov/rpdweb00/radionuclides/radon.html | accessdate =2007-08-11 }}</ref> [[Iowa]] has the highest average radon concentration in the United States; studies performed there have demonstrated a 50% increased lung cancer risk with prolonged radon exposure above the EPA's action level of 4 pCi/L.<ref name="Field">{{cite journal | last =Field | first =RW | coauthors = Steck DJ, Smith BJ et al. | title =Residential radon gas exposure and lung cancer: the Iowa Radon Lung Cancer Study | journal =American Journal of Epidemiology | volume =151 | issue =11 | pages =1091–1102 | publisher =Oxford Journals | date =June 2000 | url=http://aje.oxfordjournals.org/cgi/reprint/151/11/1091 | pmid =10873134 }}</ref><ref name="EPA Iowa">{{cite web | last =EPA | authorlink =United States Environmental Protection Agency | title =Iowa Radon Lung Cancer Study | publisher =EPA | date =June 2000 | url =http://www.epa.gov/radon/iowastudy.html | accessdate =2007-08-11 }}</ref>
=== Asbestos ===
[[Asbestos]] can cause a variety of lung diseases, including lung cancer. There is a [[synergy|synergistic]] effect between tobacco smoking and asbestos in the formation of lung cancer.<ref name="O'Reilly">{{cite journal | last=O'Reilly | first=KM | coauthors =Mclaughlin AM, Beckett WS, Sime PJ | title =Asbestos-related lung disease | journal=American Family Physician | volume=75 | issue=5 | pages=683–688 | date=March 2007 | url=http://www.aafp.org/afp/20070301/683.html | pmid=17375514 }}</ref> In the UK, asbestos accounts for 2–3% of male lung cancer deaths.<ref name="Darnton">{{cite journal | last=Darnton | first=AJ | coauthors =McElvenny DM, Hodgson JT | title =Estimating the number of asbestos-related lung cancer deaths in Great Britain from 1980 to 2000 | journal=Annals of Occupational Hygiene | volume=50 | issue=1 | pages=29–38 | date=January 2006 | url=http://annhyg.oxfordjournals.org/cgi/content/full/50/1/29 | pmid=16126764 | doi =10.1093/annhyg/mei038 }}</ref> Asbestos can also cause cancer of the [[pleura]], called [[mesothelioma]] (which is different from lung cancer).
=== Viruses ===
[[Virus]]es are known to cause lung cancer in animals<ref name="Leroux">{{cite journal | last=Leroux | first=C | coauthors=Girard N, Cottin V et al. | title=Jaagsiekte Sheep Retrovirus (JSRV): from virus to lung cancer in sheep |journal=Veterinary Research | volume=38 | issue=2 | pages=211–228 | date =Mar-April 2007 | pmid=17257570 | doi=10.1051/vetres:2006060 }}</ref><ref name="Palmarini">{{cite journal | last=Palmarini | first=M | coauthors=Fan H | title=Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer | journal=Journal of the National Cancer Institute | volume=93 | issue=21 | pages=1603–1614 | publisher=Oxford University Press | date=November 2001 | url=http://jnci.oxfordjournals.org/cgi/content/full/93/21/1603 | pmid=11698564 | doi=10.1093/jnci/93.21.1603 }}</ref> and recent evidence suggests similar potential in humans. Implicated viruses include [[human papillomavirus]],<ref name="Cheng">{{cite journal | last=Cheng | first=YW | coauthors=Chiou HL, Sheu GT et al. | title=The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women | journal=Cancer Research | volume=61 | issue=7 | pages=2799–2803 | publisher=American Association for Cancer Research | date=April 2001 | url=http://cancerres.aacrjournals.org/cgi/content/full/61/7/2799 | pmid=11306446 }}</ref> [[JC virus]],<ref name="Zheng">{{cite journal | last=Zheng | first=H | coauthors=Aziz HA, Nakanishi Y et al. | title=Oncogenic role of JC virus in lung cancer | journal=Journal of Pathology | volume=212 | issue=3 | pages=306–315 | date=May 2007 | pmid=17534844 | doi=10.1002/path.2188 }}</ref> [[SV40|simian virus 40]] (SV40), [[BK virus]] and [[cytomegalovirus]].<ref name="Giuliani">{{cite journal | last=Giuliani | first=L | coauthors=Jaxmar T, Casadio C et al. | title=Detection of oncogenic viruses (SV40, BKV, JCV, HCMV, HPV) and p53 codon 72 polymorphism in lung carcinoma | journal=Lung Cancer | volume=57 |issue=3 | pages=273–281 | date=September 2007 | pmid=17400331 | doi=10.1016/j.lungcan.2007.02.019 }}</ref> These viruses may affect the [[cell cycle]] and inhibit [[apoptosis]], allowing uncontrolled cell division.
== Pathophysiology ==
{{main|Carcinogenesis}}
Similar to many other cancers, lung cancer is initiated by activation of [[oncogene]]s or inactivation of [[tumor suppressor gene]]s.<ref name="Fong">{{cite journal | last=Fong | first=KM | coauthors=Sekido Y, Gazdar AF, Minna JD | title=Lung cancer. 9: Molecular biology of lung cancer: clinical implications | journal=Thorax | volume=58 | issue=10 | pages=892–900 | publisher=BMJ Publishing Group Ltd. | date=October 2003 | pmid=14514947 | doi=10.1136/thorax.58.10.892 }}</ref> Oncogenes are [[gene]]s that are believed to make people more susceptible to cancer. [[Proto-oncogene]]s are believed to turn into oncogenes when exposed to particular carcinogens.<ref name="Salgia">{{cite journal | last=Salgia | first=R | coauthors=Skarin AT | title=Molecular abnormalities in lung cancer | journal=Journal of Clinical Oncology | volume=16 | issue=3 | pages=1207–1217 | date=March 1998 | pmid=9508209 }}</ref> [[Mutation]]s in the ''[[Ras|K-ras]]'' proto-oncogene are responsible for 20–30% of non-small cell lung cancers.<ref name="Aviel-Ronen">{{cite journal | last=Aviel-Ronen | first=S | coauthors=Blackhall FH, Shepherd FA, Tsao MS | title=K-ras mutations in non-small-cell lung carcinoma: a review | journal=Clinical Lung Cancer | volume=8 | issue=1 | pages=30–38 | publisher=Cancer Information Group | date=July 2006 | pmid=16870043 }}</ref> [[Chromosome|Chromosomal]] damage can lead to [[loss of heterozygosity]]. This can cause inactivation of tumor suppressor genes. Damage to chromosomes 3p, 5q, 13q and 17p are particularly common in small cell lung carcinoma. The ''[[TP53]]'' tumor suppressor gene, located on chromosome 17p, is often affected.<ref name="Devereux">{{cite journal | last=Devereux | first=TR | coauthors=Taylor JA, Barrett JC | title=Molecular mechanisms of lung cancer. Interaction of environmental and genetic factors | journal=Chest | volume=109 | issue=Suppl 3 | pages=14S–19S | publisher=American College of Chest Physicians | date=March 1996 | url=http://www.chestjournal.org/cgi/reprint/109/3/14S | pmid=8598134 | doi=10.1378/chest.109.3_Supplement.14S }}</ref>
Several [[genetic polymorphism]]s are associated with lung cancer. These include polymorphisms in [[gene]]s coding for [[interleukin]]-1,<ref name="Engels">{{cite journal | last=Engels | first=EA | coauthors=Wu X, Gu J et al. | title=Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer | journal=Cancer Research | volume=67 | issue=13 | pages=6520–6527 | publisher=American Association for Cancer Research | date=July 2007 | pmid=17596594 | doi=10.1158/0008-5472.CAN-07-0370 }}</ref> [[cytochrome P450]],<ref name="Wenzlaff">{{cite journal | last =Wenzlaff | first =AS | coauthors=Cote ML, Bock CH et al. | title=CYP1A1 and CYP1B1 polymorphisms and risk of lung cancer among never smokers: a population-based study | journal=Carcinogenesis | volume=26 | issue=12 | pages=2207–2212 | publisher=Oxford University Press | date=December 2005 | pmid=16051642 | doi=10.1093/carcin/bgi191 }}</ref> [[apoptosis]] promoters such as [[caspase]]-8,<ref name="Son">{{cite journal | last=Son | first=JW | coauthors=Kang HK, Chae MH et al. | title=Polymorphisms in the caspase-8 gene and the risk of lung cancer | journal=Cancer Genetics and Cytogenetics | volume=169 | issue=2 | pages=121–127 | date=September 2006 | pmid=16938569 | doi=10.1016/j.cancergencyto.2006.04.001 }}</ref> and DNA repair molecules such as [[XRCC1]].<ref name="Yin">{{cite journal | last=Yin | first=J | coauthors=Vogel U, Ma Y et al. | title=The DNA repair gene XRCC1 and genetic susceptibility of lung cancer in a northeastern Chinese population | journal=Lung Cancer | volume=56 | issue=2 | pages=153–160 | date=May 2007 | pmid=17316890 | doi=10.1016/j.lungcan.2006.12.012 }}</ref> People with these polymorphisms are more likely to develop lung cancer after exposure to [[carcinogen]]s.
== Diagnosis ==
[[Image:Thorax pa peripheres Bronchialcarcinom li OF markiert.jpg|thumb|Chest x-ray showing a cancerous tumor in the left lung]]
Performing a [[chest x-ray]] is the first step if a patient reports symptoms that may be suggestive of lung cancer. This may reveal an obvious mass, widening of the [[mediastinum]] (suggestive of spread to [[lymph node]]s there), [[atelectasis]] (collapse), consolidation ([[pneumonia]]), or [[pleural effusion]]. If there are no x-ray findings but the suspicion is high (such as a heavy smoker with blood-stained sputum), [[bronchoscopy]] and/or a [[CT scan]] may provide the necessary information. Bronchoscopy or CT-guided [[biopsy]] is often used to identify the tumor type.<ref name="Harrison"/>
[[Image:Thorax CT peripheres Brronchialcarcinom li OF.jpg|thumb|left|CT scan showing a cancerous tumor in the left lung]]
The [[differential diagnosis]] for patients who present with abnormalities on chest x-ray includes lung cancer, as well as nonmalignant diseases. These include infectious causes such as [[tuberculosis]] or pneumonia, or inflammatory conditions such as [[sarcoidosis]]. These diseases can result in [[mediastinum|mediastinal]] [[lymphadenopathy]] or lung [[nodule (medicine)|nodules]], and sometimes mimic lung cancers.<ref name="Cancer Medicine"/> Lung cancer can also be an [[incidentaloma|incidental finding]] under the form of a [[solitary pulmonary nodule]] (also called a coin lesion) on a chest X-ray or CT scan taken for an unrelated reason.
== Prevention ==
{{see also|Smoking ban|List of smoking bans}}
Prevention is the most cost-effective means of fighting lung cancer. While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and [[smoking cessation]] is an important preventative tool in this process.<ref name="Vineis">{{cite journal | last =Vineis | first =P | coauthors =Hoek G, Krzyzanowski M et al. | title =Lung cancers attributable to environmental tobacco smoke and air pollution in non-smokers in different European countries: a prospective study | journal =Environmental Health | volume =6 | issue = | pages =7 | publisher =BioMed Central | date =February 2007 | url =http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17302981 | doi =10.1186/1476-069X-6-7 | pmid=17302981 }}</ref>
Policy interventions to decrease [[passive smoking]] in public areas such as restaurants and workplaces have become more common in many Western countries, with California taking a lead in banning smoking in public establishments in 1998. Ireland played a similar role in Europe in 2004, followed by Italy and Norway in 2005, Scotland as well as several others in 2006, England in 2007, and France in 2008. New Zealand has banned smoking in public places as of 2004. The state of [[Bhutan]] has had a complete smoking ban since 2005.<ref name="Bhutan">{{cite web | last =Pandey | first =G | title =Bhutan's smokers face public ban | publisher =BBC | date =February 2005 | url =http://news.bbc.co.uk/2/hi/south_asia/4305715.stm | accessdate =2007-09-07 }}</ref> In many countries, pressure groups are campaigning for similar bans. In 2007, [[Chandigarh]] became the first city in [[India]] to become 'smoke-free'.
Arguments cited against such bans are [[criminalisation]] of smoking, increased risk of [[smuggling]] and the risk that such a ban cannot be enforced.<ref name="Gray">{{cite journal | last =Gray | first =N | title =A global approach to tobacco policy | journal =Lung Cancer | volume =39 | issue =2 | pages =113–117 | publisher =BioMed Central | date =February 2003 | pmid =12581561 | doi =10.1016/S0169-5002(02)00456-7 }}</ref>
A 2008 study performed in over 75,000 middle-aged and elderly people demonstrated that the long-term use of supplemental multivitamins, such as vitamin C, vitamin E, and folate did not reduce the risk of lung cancer. To the contrary, the study indicates that the long term intake of high doses of vitamin E supplements may even increase the risk of lung cancer.<ref name="pmid17989343">{{cite journal |author=Slatore CG, Littman AJ, Au DH, Satia JA, White E |title=Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer |journal=Am J Respir Crit Care Med |volume=177 |issue=5 |pages=524–30 |year=2008 |pmid=17989343 |doi=10.1164/rccm.200709-1398OC}}</ref>
The [[World Health Organization]] has called for governments to institute a total ban on tobacco advertising in order to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by sixteen percent where already instituted.<ref>{{cite press release|title=UN health agency calls for total ban on tobacco advertising to protect young
|url=http://www.un.org/apps/news/story.asp?NewsID=26857 |publisher=[[United Nations]] |date=30 May 2008}}</ref>
== Screening ==
{{main|Lung cancer screening}}
[[Screening (medicine)|Screening]] refers to the use of [[medical test]]s to detect disease in asymptomatic people. Possible screening tests for lung cancer include [[chest x-ray]] or [[computed tomography]] (CT) of the chest. So far, screening programs for lung cancer have not demonstrated any clear benefit. [[Randomized controlled trial]]s are underway in this area to see if decreased long-term mortality can be directly observed from CT screening.<ref name="Gohagan">{{cite journal | last=Gohagan | first=JK | coauthors=Marcus PM, Fagerstrom RM et al. |title=Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer |journal=Lung Cancer |volume=47 |issue=1 |pages=9–15 | date=January 2005 |pmid=15603850 |doi=10.1016/j.lungcan.2004.06.007}}</ref>
== Treatment ==
Treatment for lung cancer depends on the cancer's specific cell type, how far it has [[cancer staging|spread]], and the patient's [[performance status]]. Common treatments include [[surgery]], [[chemotherapy]], and [[radiation therapy]].<ref name="Harrison"/>
=== Surgery ===
{{main|Lung cancer surgery}}
[[Image:Lung cancer.jpg|thumb|200px|right|[[Gross examination|Gross]] appearance of the cut surface of a [[pneumonectomy]] specimen containing a '''lung cancer''', here a [[Squamous cell carcinoma]] (the whitish tumor near the bronchi).]]
If investigations confirm lung cancer, CT scan and often [[positron emission tomography]] (PET) are used to determine whether the disease is localised and amenable to surgery or whether it has spread to the point where it cannot be cured surgically.
[[Blood test]]s and [[spirometry]] (lung function testing) are also necessary to assess whether the patient is well enough to be operated on. If spirometry reveals poor respiratory reserve (often due to [[chronic obstructive pulmonary disease]]), surgery may be contraindicated.
Surgery itself has an operative death rate of about 4.4%, depending on the patient's lung function and other risk factors.<ref name="Strand">{{cite journal | last =Strand | first =TE | coauthors =Rostad H, Damhuis RA, Norstein J | title =Risk factors for 30-day mortality after resection of lung cancer and prediction of their magnitude | journal =Thorax | publisher =BMJ Publishing Group | date =June 2007 | pmid =17573442 }}</ref> Surgery is usually only an option in non-small cell lung carcinoma limited to one lung, up to stage IIIA. This is assessed with medical imaging ([[computed tomography]], [[positron emission tomography]]). A sufficient pre-operative respiratory reserve must be present to allow adequate lung function after the tissue is removed.
Procedures include [[wedge resection (lung)|wedge resection]] (removal of part of a lobe), segmentectomy (removal of an anatomic division of a particular lobe of the lung), [[lobectomy (lung)|lobectomy]] (one lobe), bilobectomy (two lobes) or [[pneumonectomy]] (whole lung). In patients with adequate respiratory reserve, lobectomy is the preferred option, as this minimizes the chance of local recurrence. If the patient does not have enough functional lung for this, wedge resection may be performed.<ref name="El-Sherif">{{cite journal | last =El-Sherif | first =A | coauthors =Gooding WE, Santos R et al. | title =Outcomes of sublobar resection versus lobectomy for stage I non-small cell lung cancer: a 13-year analysis | journal =Annals of Thoracic Surgery | volume =82 | issue =2 | pages =408–415 | date =August 2006 | pmid =16863738 | doi =10.1016/j.athoracsur.2006.02.029 }}</ref> Radioactive [[iodine]] [[brachytherapy]] at the margins of wedge excision may reduce recurrence to that of lobectomy.<ref name="Fernando">{{cite journal | last =Fernando | first =HC | coauthors =Santos RS, Benfield JR et al. | title =Lobar and sublobar resection with and without brachytherapy for small stage IA non-small cell lung cancer | journal =Journal of Thoracic and Cardiovascular Surgery | volume =129 | issue =2 | pages =261–267 | date =February 2005 | pmid =15678034 | doi =10.1016/j.jtcvs.2004.09.025 }}</ref>
=== Chemotherapy ===
Small cell lung carcinoma is treated primarily with chemotherapy and radiation, as surgery has no demonstrable influence on survival. Primary chemotherapy is also given in metastatic non-small cell lung carcinoma.
The combination regimen depends on the tumor type. Non-small cell lung carcinoma is often treated with [[cisplatin]] or [[carboplatin]], in combination with [[gemcitabine]], [[paclitaxel]], [[docetaxel]], [[etoposide]] or [[vinorelbine]].<ref name="Clegg">{{cite journal | last=Clegg | first=A | coauthors=Scott DA, Hewitson P et al. | title=Clinical and cost effectiveness of paclitaxel, docetaxel, gemcitabine, and vinorelbine in non-small cell lung cancer: a systematic review | journal=Thorax | volume=57 | issue=1 | pages=20–28 | publisher=BMJ Publishing Group | date=January 2002 | pmid=11809985 | doi=10.1136/thorax.57.1.20 }}</ref> In small cell lung carcinoma, cisplatin and etoposide are most commonly used.<ref name="Murray">{{cite journal | last=Murray | first=N | coauthors=Turrisi AT | title=A review of first-line treatment for small-cell lung cancer | journal=Journal of Thoracic Oncology | volume=1 | issue=3 | pages=270–278 | date=March 2006 | pmid=17409868 }}</ref> Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, [[topotecan]] and [[irinotecan]] are also used.<ref name="Azim">{{cite journal | last=Azim | first=HA | coauthors=Ganti AK | title=Treatment options for relapsed small-cell lung cancer | journal=Anticancer drugs | volume=18 | issue=3 | pages=255–261 | date=March 2007 | pmid=17264756 | doi=10.1097/CAD.0b013e328011a547 }}</ref><ref name="MacCallum">{{cite journal | last=MacCallum | first=C | coauthors=Gillenwater HH | title=Second-line treatment of small-cell lung cancer | journal=Current Oncology Reports | volume=8 | issue=4 | pages=258–264 | date=July 2006 | pmid=17254525 | doi=10.1007/s11912-006-0030-8 }}</ref>
==== Adjuvant chemotherapy for NSCLC====
[[Adjuvant chemotherapy]] refers to the use of chemotherapy after surgery to improve the outcome. During surgery, samples are taken from the [[lymph node]]s. If these samples contain cancer, then the patient has stage II or III disease. In this situation, adjuvant chemotherapy may improve survival by up to 15%.<ref name="Winton">{{cite journal | last=Winton | first=T | coauthors=Livingston R, Johnson D et al. | title=Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer | journal=New England Journal of Medicine | volume=352 | issue=25 | pages=2589–2597 | publisher=Massachusetts Medical Society | date=June 2005 | pmid=15972865 | doi=10.1056/NEJMoa043623 }}</ref><ref name="Douillard">{{cite journal | last=Douillard | first=JY | coauthors=Rosell R, De Lena M et al. | title=Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association <nowiki>[ANITA]</nowiki>): a randomised controlled trial | journal=Lancet Oncology | volume=7 | issue=9 | pages=719–727 | publisher=Elsevier | date=September 2006 | pmid=16945766 | doi=10.1016/S1470-2045(06)70804-X }}</ref> Standard practice is to offer platinum-based chemotherapy (including either cisplatin or carboplatin).<ref name="Tsuboi">{{cite journal | last=Tsuboi | first=M | coauthors=Ohira T, Saji H et al. | title=The present status of postoperative adjuvant chemotherapy for completely resected non-small cell lung cancer | journal=Ann Thorac Cardiovasc Surg | volume=13 | issue=2 | pages=73–77 | date=April 2007 | url=http://www.atcs.jp/pdf/2007_13_2/73.pdf | format=PDF | pmid=17505412 }}</ref>
Adjuvant chemotherapy for patients with stage IB cancer is controversial as clinical trials have not clearly demonstrated a survival benefit.<ref name="Horn">{{cite journal | last =Horn | first =L | coauthors = Sandler AB, Putnam JB Jr, Johnson DH | title =The rationale for adjuvant chemotherapy in stage I non-small cell lung cancer | journal =Journal of Thoracic Oncology | volume =2 | issue =5 | pages =377–383 | date =May 2007 | pmid =17473651 | doi =10.1097/01.JTO.0000268669.64625.bb }}</ref><ref name="Wakelee">{{cite journal | last =Wakelee | first =HA | coauthors =Schiller JH, Gandara DR | title =Current status of adjuvant chemotherapy for stage IB non-small-cell lung cancer: implications for the New Intergroup Trial | journal =Clinical Lung Cancer | volume =8 | issue =1 | pages =18–21 | publisher =Cancer Information Group | date =July 2006 | pmid =16870041 }}</ref> Trials of preoperative chemotherapy ([[neoadjuvant chemotherapy]]) in resectable non-small cell lung carcinoma have been inconclusive.<ref name="Clinical evidence">{{cite book | last =BMJ | authorlink =British Medical Journal | title =Clinical Evidence Concise | publisher =BMJ Publishing Group | date =December 2005 | pages =486–488 | isbn =1-905545-00-2 | issn=1475-9225 }}</ref>
=== Radiotherapy ===
[[Radiation therapy|Radiotherapy]] is often given together with chemotherapy, and may be used with curative intent in patients with non-small cell lung carcinoma who are not eligible for surgery. This form of high intensity radiotherapy is called ''radical radiotherapy''. A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), where a high dose of radiotherapy is given in a short time period.<ref name="Saunders"/> For small cell lung carcinoma cases that are potentially curable, in addition to chemotherapy, chest radiation is often recommended.<ref name="Wagner">{{cite journal | last =Wagner | first =H | title =Radiation therapy in the management of limited small cell lung cancer: when, where, and how much? | journal =Chest | volume =113 | issue =Suppl. 1 | pages =92S–100S | publisher =American College of Chest Physicians | date =January 1998 | url =http://www.chestjournal.org/cgi/reprint/113/1/92S | pmid =9438697 | doi =10.1378/chest.113.1_Supplement.92S }}</ref> The use of adjuvant thoracic radiotherapy following curative intent surgery for non-small cell lung carcinoma is not well established and controversial. Benefits, if any, may only be limited to those in whom the tumor has spread to the [[mediastinal]] [[lymph nodes]].<ref name="PORT Meta-analysis Trialists Group">{{cite journal |author= |title=Postoperative radiotherapy for non-small cell lung cancer |journal=Cochrane database of systematic reviews (Online) |volume= |issue=2 |pages=CD002142 |year=2005 |pmid=15846628 |url=http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD002142/frame.html |doi=10.1002/14651858.CD002142.pub2}}</ref><ref name="Lally">{{cite journal | last=Lally | first=BE | coauthors=Zelterman D, Colasanto JM et al. | title=Postoperative Radiotherapy for Stage II or III Non–Small-Cell Lung Cancer Using the Surveillance, Epidemiology, and End Results Database | journal=Journal of Clinical Oncology | volume=24 | issue=19 | pages=2998–3006 | publisher=John Wiley & Sons | date=July 2006 | url=http://jco.ascopubs.org/cgi/content/full/24/19/2998 | pmid=16769986 | doi=10.1200/JCO.2005.04.6110}}</ref>
For both non-small cell lung carcinoma and small cell lung carcinoma patients, smaller doses of radiation to the chest may be used for symptom control ([[palliative care|palliative]] radiotherapy). Unlike other treatments, it is possible to deliver palliative radiotherapy without confirming the [[histology|histological]] diagnosis of lung cancer.
[[Brachytherapy]] (localized radiotherapy) may be given directly inside the airway when cancer affects a short section of bronchus.<ref name="Raben">{{cite journal | last=Raben | first=A | coauthors=Mychalczak B | title=Brachytherapy for non-small cell lung cancer and selected neoplasms of the chest | journal=Chest | volume=112 | issue=Suppl. 4 | pages=276S–286S | publisher=American College of Chest Physicians | date=October 1997 | url=http://www.chestjournal.org/cgi/reprint/112/4_Supplement/276S | pmid=9337304 | doi=10.1378/chest.112.4_Supplement.276S }}</ref> It is used when inoperable lung cancer causes blockage of a large airway.<ref name="Celebioglu">{{cite journal | last=Celebioglu | first=B | coauthors=Gurkan OU, Erdogan S et al. | title=High dose rate endobronchial brachytherapy effectively palliates symptoms due to inoperable lung cancer | journal=Japanese Journal of Clinical Oncology | volume=32 | issue=11 | pages=443–448 | publisher=Oxford University Press | date=November 2002 | url=http://jjco.oxfordjournals.org/cgi/content/full/32/11/443 | pmid=12499415 }}</ref>
Patients with limited stage small cell lung carcinoma are usually given prophylactic cranial irradiation (PCI). This is a type of radiotherapy to the brain, used to reduce the risk of [[metastasis]].<ref name="Ng">{{cite journal | last=Ng | first=M | coauthors=Chong J, Milner A et al. | title =Tolerability of accelerated chest irradiation and impact on survival of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer: review of a single institution's experience | journal=Journal of Thoracic Oncology | volume=2 | issue=6 | pages=506–513 | publisher=International Association for the Study of Lung Cancer | date=June 2007 | pmid=17545845 | doi=10.1097/JTO.0b013e318060095b }}</ref> More recently, PCI has also been shown to be beneficial in those with extensive small cell lung cancer. In patients whose cancer has improved following a course of [[chemotherapy]], PCI has been shown to reduce the cumulative risk of brain [[metastases]] within one year from 40.4% to 14.6%.<ref name="Slotman">{{cite journal | last=Slotman | first=B | coauthors=Faivre-Finn C, Kramer G et al. | title = Prophylactic cranial irradiation in extensive small-cell lung cancer | journal=New England Journal of Medicine | volume=357 | issue=7 | pages=664–672 | date=August 2007 | url=http://content.nejm.org/cgi/content/full/357/7/664 | accessdate=2008-07-10 | pmid=17699816 | doi=10.1056/NEJMoa071780 }}</ref>
Recent improvements in targeting and imaging have led to the development of extracranial stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiation therapy, very high doses are delivered in a small number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical [[comorbidities]].<ref name="Hof">{{cite journal | last=Hof | first=H | coauthors=Muenter M, Oetzel D et al. | title=Stereotactic single-dose radiotherapy (radiosurgery) of early stage nonsmall-cell lung cancer (NSCLC) | journal=Cancer | volume=110 | issue=1 | pages=148–155 | publisher=Wiley InterScience | date=July 2007 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/114265991/PDFSTART | accessdate=2008-07-10 | pmid=17516437 | doi=10.1002/cncr.22763 }}</ref>
=== Interventional radiology ===
[[Radiofrequency ablation]] should currently be considered an investigational technique in the treatment of bronchogenic carcinoma. It is done by inserting a small heat probe into the tumor to kill the tumor cells.<ref name="Simon">{{cite journal | last =Simon | first =CJ | coauthors =Dupuy DE, DiPetrillo TA et al. | title =Pulmonary radiofrequency ablation: long-term safety and efficacy in 153 patients | journal =Radiology | volume =243 | issue =1 | pages =268–275 | date =April 2007 | pmid =17392258 | doi =10.1148/radiol.2431060088 }}</ref>
=== Targeted therapy ===
In recent years, various molecular targeted therapies have been developed for the treatment of advanced lung cancer. [[Gefitinib]] (Iressa) is one such drug, which targets the [[tyrosine kinase]] domain of the [[epidermal growth factor receptor]] (EGF-R) which is expressed in many cases of non-small cell lung carcinoma. It was not shown to increase survival, although females, Asians, non-smokers and those with [[bronchioloalveolar carcinoma]] appear to derive the most benefit from gefitinib.<ref name="Raz"/>
[[Erlotinib]] (Tarceva), another tyrosine kinase inhibitor, has been shown to increase survival in lung cancer patients<ref name="Feld">{{cite journal | last=Feld | first=R | coauthors=Sridhar SS, Shepherd FA et al. | title=Use of the epidermal growth factor receptor inhibitors gefitinib and erlotinib in the treatment of non-small cell lung cancer: a systematic review | journal=Journal of Thoracic Oncology | volume=1 | issue=4 | pages=367–376 | publisher=International Association for the Study of Lung Cancer | date=May 2006 | pmid=17409886 | doi=10.1097/01243894-200605000-00018 }}</ref> and has recently been approved by the FDA for second-line treatment of advanced non-small cell lung carcinoma. Similar to gefitinib, it appeared to work best in females, Asians, non-smokers and those with bronchioloalveolar carcinoma.<ref name="Bencardino">{{cite journal | last=Bencardino | first=K | coauthors=Manzoni M, Delfanti S et al. | title=Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small-cell lung cancer: results and open issues | journal=Internal and Emergency Medicine | volume=2 | issue=1 | pages=3–12 | date=March 2007 | pmid=17551677 | doi=10.1007/s11739-007-0002-5 }}</ref>
The [[angiogenesis inhibitor]] [[bevacizumab]] (in combination with [[paclitaxel]] and [[carboplatin]]) improves the survival of patients with advanced non-small cell lung carcinoma.<ref name="Sandler">{{cite journal | last=Sandler| first=A | coauthors=Gray R, Perry M et al. | title=Paclitaxel–carboplatin alone or with bevacizumab for non–small cell lung cancer | journal=New England Journal of Medicine | volume=355 | issue=24 | pages=2542–2550 | publisher=Massachusetts Medical Society | date=December 2006 | pmid=17167137 | doi=10.1056/NEJMoa061884 }}</ref> However this increases the risk of lung bleeding, particularly in patients with [[squamous cell carcinoma]].
Advances in cytotoxic drugs,<ref name="Edelman">{{cite journal | last =Edelman | first =MJ | title =Novel cytotoxic agents for non-small cell lung cancer | journal =Journal of Thoracic Oncology | volume =1 | issue =7 | pages =752–755 | date =September 2006 | pmid=17409954 }}</ref> [[pharmacogenetics]]<ref name="Danesi">{{cite journal | last =Danesi | first =R | coauthors =Pasqualetti G, Giovannetti E, Del Tacca M | title =The role of pharmacogenetics in adjuvant treatment of non-small cell lung cancer | journal =Journal of Thoracic Oncology | volume =2 | issue =5 Suppl. | pages =S27–S30 | date =May 2007 | pmid=17457227 | doi =10.1097/01.JTO.0000268638.10332.07}}</ref> and targeted drug design<ref name="Blackhall">{{cite journal | last =Blackhall | first =FH | coauthors =Shepherd FA | title =Small cell lung cancer and targeted therapies | journal =Current Opinion in Oncology | volume =19 | issue =2 | pages =103–108 | publisher = | date =March 2007 | pmid = 17272981 }}</ref> show promise. A number of targeted agents are at the early stages of clinical research, such as [[COX-2 inhibitor|cyclo-oxygenase-2 inhibitors]],<ref>{{cite journal | last =Lee | first =JM | coauthors =Mao JT, Krysan K, Dubinett SM | title =Significance of cyclooxygenase-2 in prognosis, targeted therapy and chemoprevention of NSCLC | journal =Future Oncology | volume =2 | issue =2 | pages =149–153 | date =April 2007 | pmid =17381414 | doi =10.2217/14796694.3.2.149 }}</ref> the [[apoptosis]] promoter [[exisulind]],<ref>{{cite journal | last =Whitehead | first =CM | coauthors =Earle KA, Fetter J et al. | title =Exisulind-induced Apoptosis in a Non-Small Cell Lung Cancer Orthotopic Lung Tumor Model Augments Docetaxel Treatment and Contributes to Increased Survival | journal =Molecular Cancer Therapeutics | volume =2 | pages =479–488 | publisher =American Association for Cancer Research | date =May 2003 | url =http://mct.aacrjournals.org/cgi/content/full/2/5/479 | pmid = 12748310 }}</ref> [[proteasome inhibitor]]s,<ref name="Scagliotti">{{cite journal | last =Scagliotti | first =G | title =Proteasome inhibitors in lung cancer | journal =Critical Reviews in Oncology/Haematology | volume =58 | issue =3 | pages =177–189 | date =June 2006 | pmid = 16427303 | doi =10.1016/j.critrevonc.2005.12.001 }}</ref> [[bexarotene]]<ref name="Dragnev">{{cite journal | last =Dragnev | first =KH | coauthors =Petty WJ, Shah SJ et al. | title =A proof-of-principle clinical trial of bexarotene in patients with non-small cell lung cancer | journal =Clinical Cancer Research | volume =13 | issue =6 | pages =1794–1800 | publisher =American Association for Cancer Research | date =March 2007 | pmid = 17363535 | doi =10.1158/1078-0432.CCR-06-1836 }}</ref> and vaccines.<ref>{{cite journal | last =Albright | first =C | coauthors =Garst J | title =Vaccine therapy in non-small cell lung cancer | journal =Current Oncology Reports | volume=9 | issue=4 | pages=241–246 | date=July 2007 | pmid =17588347 | doi =10.1007/s11912-007-0029-9 }}</ref> Future areas of research include [[ras]] [[proto-oncogene]] inhibition, [[phosphoinositide 3-kinase]] inhibition, [[histone deacetylase]] inhibition, and [[tumor suppressor gene]] replacement.<ref>{{cite journal | last=Sun | first=S | coauthors=Schiller JH, Spinola M, Minna JD | title=New molecularly targeted therapies for lung cancer | journal=Journal of Clinical Investigation | volume=117 | issue=10 | pages=2740–2750 | publisher=American Society for Clinical Investigation | date=October 2007 | url=http://www.jci.org/cgi/content/full/117/10/2740 | pmid=17909619 | doi=10.1172/JCI31809 }}</ref>
== Prognosis ==
{{main|Non-small cell lung carcinoma staging|Manchester score}}
Prognostic factors in non- small-cell lung cancer include presence or absence of pulmonary symptoms, [[tumor]] size, cell type ([[histology]]), degree of spread [[staging (pathology)|(stage)]] and [[metastases]] to multiple [[lymph nodes]], and vascular invasion. For patients with inoperable disease, prognosis is adversely affected by poor [[performance status]] and weight loss of more than 10%.<ref>
[http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-lung/HealthProfessional/page2 National Cancer Institute PDQ for Professionals].</ref> Prognostic factors in small-cell lung cancer include [[performance status]], [[gender]], stage of disease, and involvement of the [[central nervous system]] or [[liver]] at the time of [[diagnosis]]. <ref>{{cite web |publisher=National Cancer Institute |url=http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional |title=PDQ for Professionals |accessdate=}}</ref>
For non-small cell lung carcinoma, prognosis is generally poor. Following complete surgical resection of stage IA disease, five-year survival is 67%. With stage IB disease, five-year survival is 57%.<ref name="Mountain">{{cite journal | last =Mountain | first =CF | title =Revisions in the international system for staging lung cancer | journal =Chest | volume =111 | pages =1710–1717 | publisher =American College of Chest Physicians | date=1997 | url=http://www.chestjournal.org/cgi/reprint/111/6/1710 | format = PDF | pmid = 9187198 | doi =10.1378/chest.111.6.1710 }}</ref> The 5-year survival rate of patients with stage IV NSCLC is about 1%.<ref name="Merck">{{cite web | title=Lung Carcinoma: Tumors of the Lungs | publisher = Merck Manual Professional Edition, Online edition | url=http://www.merck.com/mmpe/sec05/ch062/ch062b.html#sec05-ch062-ch062b-1405 | accessdate=2007-08-15 }}</ref>
For small cell lung carcinoma, prognosis is also generally poor. The overall five-year survival for patients with SCLC is about 5%.<ref name="Harrison"/> Patients with extensive-stage SCLC have an average five-year survival rate of less than 1%. The [[median]] survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%.<ref name="Merck"/>
According to data provided by the [[National Cancer Institute]], the median age of incidence of lung cancer is 70 years, and the median age of death by lung cancer 71 years.<ref>{{cite web |url=http://seer.cancer.gov/cgi-bin/csr/1975_2002/search.pl#results |title=SEER Cancer Statistics Review 1975-2002 - Search |accessdate=2007-11-18 |format= |work=}}</ref>
==Epidemiology==
[[Image:Lung cancer US distribution.gif|right|thumb|300px|Lung cancer distribution in the [[United States]]]]
Worldwide, lung cancer is the most common cancer in terms of both incidence and mortality with 1.35 million new cases per year and 1.18 million deaths, with the highest rates in Europe and North America.<ref>{{cite web | title=Commonly diagnosed cancers worldwide | publisher=Cancer Research UK | date=Apr 2005 | url=http://info.cancerresearchuk.org/cancerstats/geographic/world/commoncancers/ | accessdate=2008-01-11 }}</ref> The population segment most likely to develop lung cancer is over-fifties who have a history of smoking. Lung cancer is the second most commonly occurring form of cancer in most western countries, and it is the leading cancer-related cause of death. Although the rate of men dying from lung cancer is declining in western countries, it is actually increasing for women due to the increased takeup of smoking by this group. Among lifetime non-smokers, men have higher age-standardized lung cancer death rates than women.
Not all cases of lung cancer are due to smoking, but the role of [[passive smoking]] is increasingly being recognized as a risk factor for lung cancer, leading to policy interventions to decrease undesired exposure of non-smokers to others' tobacco smoke. Emissions from automobiles, factories and power plants also pose potential risks.<ref name="Kabir"/><ref name="Chiu"/><ref name="Parent">{{cite journal | last=Parent | first=ME | coauthors=Rousseau MC, Boffetta P et al. | title=Exposure to diesel and gasoline engine emissions and the risk of lung cancer | journal=American Journal of Epidemiology | volume=165 | issue=1 | pages=53–62 | date=January 2007 | pmid=17062632 | doi=10.1093/aje/kwj343 }}</ref>
[[Eastern Europe]] has the highest lung cancer mortality among men, while northern Europe and the U.S. have the highest mortality among women.Lung cancer incidence is currently less common in developing countries.<ref>{{cite web | title=Gender in lung cancer and smoking research | publisher=[[World Health Organization]] | date=2004 | url=http://www.who.int/gender/documents/en/lungcancerlow.pdf | format=PDF | accessdate=2007-05-26 }}</ref> With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China<ref>{{cite journal | last=Liu | first=BQ | coauthors=Peto R, Chen ZM et al. | title=Emerging tobacco hazards in China: 1. Retrospective proportional mortality study of one million deaths | journal=British Medical Journal | volume=317 | issue=7170 | pages=1411–1422 | date=November 1998 | url=http://www.bmj.com/cgi/content/full/317/7170/1411 | pmid=9822393 }}</ref> and India.<ref>{{cite journal | last=Behera | first=D | coauthors=Balamugesh T | title=Lung cancer in India | journal=Indian Journal of Chest Diseases and Allied Sciences | volume=46 | issue=4 | pages=269–281 | date=2004 | pmid=15515828 }}</ref>
Lung cancer incidence (by country) has an inverse correlation with [[sunlight]] and [[Ultraviolet|UVB]] exposure. One possible explanation is a preventative effect of [[vitamin D]] (which is produced in the skin on exposure to sunlight).<ref>{{cite journal | last=Mohr | first=SB | coauthors=Garland CF, Gorham ED et al. | title=Could ultraviolet B irradiance and vitamin D be associated with lower incidence rates of lung cancer? | journal=Journal of Epidemiology and Community Health | volume=62 | issue=1 | pages=69–74 | year=2008 | pmid=18079336 | doi=10.1136/jech.2006.052571 }}</ref>
==History==
Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761.<ref>{{cite book | last=Morgagni | first=Giovanni Battista | title=De sedibus et causis morborum per anatomen indagatis | date=1761 |url=http://books.google.ca/books?id=A3IFAAAAQAAJ&printsec=frontcover&dq=editions:0gslDCsk4Fm2hLne }}</ref> Different aspects of lung cancer were described further in 1810.<ref>{{cite book | last=Bayle | first=Gaspard-Laurent | title=Recherches sur la phtisie pulmonaire |place=Paris |language=French | date=1810 }}</ref> Malignant lung tumors made up only 1% of all cancers seen at autopsy in 1878, but had risen to 10–15% by the early 1900s.<ref name="Witschi">{{cite journal | last=Witschi | first=H | title=A short history of lung cancer | journal=Toxicological Sciences | volume=64 | issue=1 | pages=4–6 | date=November 2001 | url=http://toxsci.oxfordjournals.org/cgi/content/full/64/1/4 |pmid=11606795 | doi=10.1093/toxsci/64.1.4 }}</ref> Case reports in the medical literature numbered only 374 worldwide in 1912,<ref>{{cite book|author=Adler, I |year=1912 |title=Primary Malignant Growths of the Lungs and Bronchi |place= New York |publisher=Longmans, Green, and Company |oclc=14783544}}, cited in {{cite journal |author=Spiro SG, Silvestri GA |title=One hundred years of lung cancer |journal=Am. J Respir Crit Care Med |volume=172 |issue=5 |pages=523–529 |year=2005 |pmid=15961694 |doi=10.1164/rccm.200504-531OE}}</ref> but a review of autopsies showed that the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952.<ref name="Grannis">{{cite web | last =Grannis | first =FW |title=History of cigarette smoking and lung cancer | publisher =smokinglungs.com | url =http://www.smokinglungs.com/cighist.htm | accessdate =2007-08-06 }}</ref> In [[Germany]], in 1929 physician Fritz Lickint recognized the link between smoking and lung cancer,<ref name="Witschi"/> which led to an aggressive anti-smoking campaign.<ref name="Proctor">{{cite book | last =Proctor | first =R | title =The Nazi War on Cancer | publisher =Princeton University Press | date =2000 | location = | pages =173–246 | isbn=0-691-00196-0 }}</ref> The [[British Doctors Study]], published in the 1950s, was the first solid [[epidemiology|epidemiological]] evidence of the link between lung cancer and smoking.<ref name="Doll">{{cite journal | last =Doll | first =R | coauthors =Hill AB | title =Lung cancer and other causes of death in relation to smoking; a second report on the mortality of British doctors | journal =British Medical Journal | volume =2 | issue =5001 | pages =1071–1081 | date =November 1956 | pmid = 13364389 }}</ref> As a result, in 1964 the [[Surgeon General of the United States]] recommended that smokers should stop smoking.<ref>{{citation | author=US Department of Health Education and Welfare | title =Smoking and health: report of the advisory committee to the Surgeon General of the Public Health Service | place=Washington, DC | publisher =US Government Printing Office | date =1964 }}</ref>
The connection with [[radon]] gas was first recognized among miners in the [[Ore Mountains (Germany)|Ore Mountains]] near [[Schneeberg, Saxony]]. [[Silver]] has been mined there since 1470, and these mines are rich in [[uranium]], with accompanying [[radium]] and radon gas. Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s and an estimated 75% of former miners died from lung cancer. Despite this discovery, mining continued into the 1950s due to the [[USSR]]'s demand for uranium.<ref name="Greaves">{{cite book | last =Greaves | first =M | title =Cancer: the Evolutionary Legacy | publisher =Oxford University Press | date =2000 | pages =196–197 | isbn=0-19-262835-6 }}</ref>
=== Treatment ===
The first successful [[pneumonectomy]] for lung cancer was carried out in 1933 <ref>{{cite book | author=Office of the Home Secretary | title =Biographical Memoirs | publisher =National Academy of Sciences | date =1976 | isbn=0-309-02349-1 }}</ref> and initially, pneumonectomy was the surgical treatment of choice.<ref name="Edwards">{{cite journal | last =Edwards | first =AT | title =Carcinoma of the bronchus | journal =Thorax | volume =1 | pages =1–25 | date =1946 }}</ref> However, with improvements in [[cancer staging]] and surgical techniques, [[lobectomy (lung)|lobectomy]] with [[lymph node]] dissection has now become the treatment of choice.<ref>{{cite journal | last =Scott | first =WJ | coauthors=Howington J, Movsas B | title =Treatment of stage II non-small cell lung cancer | journal =Chest | volume =123 | issue=Suppl. 1 | pages =188S–201S | publisher =American College of Chest Physicians | date =January 2003 | url =http://www.chestjournal.org/cgi/content/full/123/1_suppl/188S | pmid =12527579 | doi =10.1378/chest.123.1_suppl.188S }}</ref><ref>{{cite journal | last =Smythe | first =WJ | title =Treatment of stage I non-small cell lung carcinoma | journal =Chest | volume =123 | issue=Suppl. 1 | pages =181S–187S | publisher =American College of Chest Physicians | date =January 2003 | url =http://www.chestjournal.org/cgi/content/full/123/1_suppl/181S | pmid =12527578 | doi =10.1378/chest.123.1_suppl.181S }}</ref>
Palliative [[radiotherapy]] has been used since the 1940s.<ref name="Edwards"/> Radical radiotherapy, initially used in the 1950s, was an attempt to use larger radiation doses in patients with relatively early stage lung cancer, but who were otherwise unfit for surgery.<ref>{{cite journal | last =Kabela | first =M | title =Experience with radical irradiation of bronchial cancer | journal =Ceskoslovenská Onkológia | volume =3 | issue=2 | pages =109–115 | date =1956 | pmid =13383622 }}</ref> In 1997, continuous hyperfractionated accelerated radiotherapy (CHART) was seen as an improvement over conventional radical radiotherapy.<ref name="Saunders">{{cite journal | last =Saunders | first =M | coauthors=Dische S, Barrett A et al. | title =Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial | journal =Lancet | volume =350 | issue=9072 | pages =161–165 | publisher =Elsevier | date =July 1997 | pmid =9250182 | doi =10.1016/S0140-6736(97)06305-8 }}</ref>
With small cell lung carcinoma, initial attempts in the 1960s at surgical resection<ref>{{cite journal | last=Lennox | first=SC | coauthors=Flavell G, Pollock DJ et al. | title=Results of resection for oat-cell carcinoma of the lung | journal=Lancet | volume=2 | issue=7575 | pages=925–927 | publisher=Elsevier | date=November 1968 | pmid=4176258 }}</ref> and radical radiotherapy<ref>{{cite journal | last=Miller | first=AB | coauthors= Fox W, Tall R | title=Five-year follow-up of the Medical Research Council comparative trial of surgery and radiotherapy for the primary treatment of small-celled or oat-celled carcinoma of the bronchus | journal=Lancet | volume=2 | issue=7619 | pages=501–505 | publisher=Elsevier | date=September 1969 | pmid=4184834 }}</ref> were unsuccessful. In the 1970s, successful chemotherapy regimens were developed.<ref>{{cite journal | last=Cohen | first=M | coauthors= Creaven PJ, Fossieck BE Jr et al. | title=Intensive chemotherapy of small cell bronchogenic carcinoma | journal=Cancer Treatment Reports | volume=61 | issue=3 | pages=349–354 | date=1977 | pmid=194691 }}</ref>
== References ==
<!--See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for an explanation of how to generate footnotes using the <ref(erences/)> tags-->
{{reflist|2}}
== External links ==
* [http://www.chestradiology.net/ Chest Radiology] Lung cancer tutorial
* {{dmoz|Health/Conditions_and_Diseases/Cancer/Lung/}}
* [http://www.lungcancer.org/ LungCancer.org] - free resources and support services
* [http://www.cancer.gov/cancertopics/types/lung National Cancer Insitute]
* [http://web.archive.org/web/20060211201310/http://www-cie.iarc.fr/htdocs/indexes/vol83index.html Tobacco Smoke and Involuntary Smoking, Summary of Data Reported and Evaluation 2004] by the [[International Agency for Research on Cancer|IARC]]
* [http://www.nci.nih.gov/cancerinfo/types/lung Lung Cancer Articles & Information] Stop Smoking Articles & Information at [[National Institutes of Health]]
{{Respiratory tract neoplasia}}
{{featured article}}
[[Category:Pulmonology]]
[[Category:Types of cancer]]
[[Category:Lung cancer| ]]
[[ar:سرطان الرئة]]
[[bn:ফুসফুসের ক্যান্সার]]
[[zh-min-nan:Hì-gâm]]
[[bs:Rak pluća]]
[[bg:Рак на белия дроб]]
[[ca:Càncer de pulmó]]
[[da:Lungekræft]]
[[de:Bronchialkarzinom]]
[[es:Cáncer de pulmón]]
[[eu:Birikako minbizi]]
[[fr:Cancer du poumon]]
[[ko:폐암]]
[[hr:Rak pluća]]
[[id:Kanker paru-paru]]
[[is:Lungnakrabbamein]]
[[it:Tumore del polmone]]
[[he:סרטן הריאה]]
[[la:Cancer pulmonum]]
[[ms:Penyakit barah paru-paru]]
[[nl:Longkanker]]
[[ja:肺癌]]
[[no:Lungekreft]]
[[pl:Rak płuca]]
[[pt:Câncer de pulmão]]
[[qu:Surq'an phiru unquy]]
[[ru:Злокачественные новообразования лёгких]]
[[simple:Lung cancer]]
[[sh:Rak pluća]]
[[fi:Keuhkosyöpä]]
[[sv:Lungcancer]]
[[vi:Ung thư phổi]]
[[tr:Akciğer kanseri]]
[[yi:לונגען קענסער]]
[[zh:肺癌]]